Extrapulmonary Manifestations Of Sarcoidosis Research Articles

Characteristics of patients with sarcoidosis who referred to a pulmonologist during the COVID-19 pandemic

Introduction. During the COVID-19 pandemic, the first experience was gained in managing patients with sarcoidosis in the face of a dangerous viral infection, a combination of two diseases and vaccination against COVID-19. Publications on this issue remain ambiguous, which made it relevant to assess the management of patients with sarcoidosis during a pandemic and the features of vaccination of these patients.Aim. To assess the condition of patients with sarcoidosis who turned to a pulmonologist during the pandemic, to compare the parameters of patients with sarcoidosis who had and did not have COVID-19, with mild and severe course, as well as to evaluate the effectiveness and safety of vaccination.Materials and methods. The study was a retrospective, observational, non-interventional study. We included 299 patients who visited a pulmonologist in 176 (58.9%) of whom developed COVID-19 and 123 (41.1%) did not have a viral disease. Information on survivors of COVID-19 was collected using the COVIZ application. Data summarization and statistical processing were carried out using the SPPS-18 program (IBM) p < 0.05 values were considered statistically significant.Research results. Comparison of data of patients with sarcoidosis who fell ill and did not become ill with COVID-19 during the pandemic period showed that those who fell ill with this viral infection were significantly younger, more often had extrapulmonary manifestations of sarcoidosis. Patients did not differ in the radiation stage of sarcoidosis, the frequency of Löfgren’s syndrome, and the frequency of familial cases of granulomatosis. The use of methotrexate was accompanied by a higher incidence of COVID-19, the probability of getting sick was more than 3 times higher (OR = 3.39; 95% CI 1.12–10.28). Among those who received GCS (n = 49), those who received a dose of 10 mg prednisolone equivalent and above (OR = 12.056; CI95% 2.12–68.5) were more likely to develop COVID-19. The risk of developing COVID-19 in those who were not vaccinated was significantly higher than in those who received the vaccine after a viral illness (OR = 2.50; CI95% 1.75–3.58). One case of death is presented.Conclusion. A retrospective analysis of cases of sarcoidosis during the COVID-19 pandemic indicated a favorable course of both diseases when combined. Negative prognostic factors were the use of immunosuppressive therapy for sarcoidosis and severe comorbidities of the cardiovascular system. Vaccination against COVID-19 was effective and safe in patients with pulmonary sarcoidosis.

Editorial introductions.

Current Opinion in Pulmonary Medicine was launched in 1995. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of pulmonary medicine is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editors and Section Editors for this issue. EDITORS IN CHIEF Daniel A CulverDaniel A CulverDaniel A Culver, DO FCCP, graduated from The Ohio State University, USA, and then received his Doctor of Osteopathic Medicine degree from Heritage Ohio University College of Osteopathic Medicine, USA. He completed a rotating internship at South Pointe Hospital prior to Internal Medicine Residency and Pulmonary & Critical Care Medicine Fellowship at Cleveland Clinic, USA, where he has been a Staff Physician since 2005. Dr Culver is currently Chair of the Department of Pulmonary Medicine at Cleveland Clinic, and is the president of the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG). His clinical and research interests focus on diffuse parenchymal lung disease, and also on extrapulmonary manifestations of sarcoidosis. He is also engaged in teaching and training fellows and other trainees. Marjolein DrentMarjolein DrentProf. Marjolein Drent is currently guest senior researcher at the ILD Center of Excellence, St. Antonius Hospital, Nieuwegein, the Netherlands. She was a pulmonologist and member of the Center from 2015 till August 2022. In 2005, she was appointed as Professor of Interstitial Lung Diseases (ILD) at the Department of Pharmacology and Toxicology of the Faculty of Health and Life Sciences of the Maastricht University, the Netherlands. Her oration was entitled: ‘Breathtaking Inspirations’. She retired from that position in July, 2022 and is currently professor emeritus. She is also emeritus president of WASOG (World Association of Sarcoidosis and Other Granulomatous Diseases), and is now Chief Editor of Current Opinion in Pulmonary Medicine and associate editor of Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. Furthermore, she is co-editor/guest editor of several sarcoidosis articles in international journals, and is a reviewer for a number of international journals. She has (co-) authored over 450 papers and book chapters. She has been deeply involved in the last decades with several educational assignments, organization of postgraduate courses, national and international congresses, guideline development, as well as clinical trials. She is widely recognized as the co-editor of several ILD and sarcoidosis-related e-learning modules for pulmonologists and ILD nurses. Prof. Drent is a sought-after speaker and has acted as such on more than 300 occasions, nationally and internationally. Her scientific interest is focused on sarcoidosis, fibrotic lung diseases, drug-induced ILD, quality of life, fatigue, and work-related sequalae. She is a member of the Foundation for Sarcoidosis Research (FSR) Advisory Board; the founder and chair of the ILD Care Foundation (ILD, including sarcoidosis; www.ildcare.nl); co-founder and member of the advisory board of the Dutch Pulmonary Fibrosis Patient Association; and honorary member of Sarcoidose.nl (Dutch Sarcoidosis Patient Association). She has been the (co)promotor of 14 PhD students. In 2012 she was nominated for the ‘World Sarcoidosis Person of the Year Award’ Dublin, Ireland, for her tireless research in defining the often immense psychological burden faced by patients and their families. She is an avid ambassador for Compassion for Care and the Youth Smoking Prevention Foundation. In 2016 she was appointed an Officer in the Order of Orange Nassau by Royal Decree. In 2022 she won the European Respiratory Society (ERS) Lifetime Achievement Award ILD 2022 (Assembly 12) for her outstanding contributions to the field of ILD. SECTION EDITORS Sadia BenzaquenSadia BenzaquenSadia Benzaquen, MD, FACP, FCCP, ATSF, DAABIP is the Chairman of Pulmonary, Critical Care, Sleep and Allergy at Einstein Medical Center, Philadelphia, USA. He is a Professor of Medicine at the Sidney Kimmel Medical College at Jefferson University, Philadelphia, USA. He is an expert in the interventional pulmonology field with extensive research and publications in lung cancer, pleural disease and ILD. Sara TomasettiSara TomasettiSara Tomassetti is currently Associate Professor of Respiratory Medicine at Florence University, Italy, and Head of Interventional Pulmonology Unit at Careggi University Hospital, Florence, Italy. She has extensive experience in all aspects of interstitial lung diaseses and interventional pulmonology, including cryobiopsy. She is a faculty member of the European Respiratory Society, and BOND National member for Italy of the European Association for Bronchology and Interventional Pulmonology. From a clinical research perspective, she has been the primary investigator (PI) of several sponsored and investigator initiated clinical trials on diagnosis and treatemnt of ineterstiatial lung diseases and idiopathic pulmonary fibrosis. She publishes on clinical research aspects of interstitial lung diseases and interventional pulmonology. She regularly reviews research and clinical manuscripts for international journals.

BILATERAL INGUINAL LYMPHADENOPATHY AS THE EXTRAPULMONARY PRESENTATION OF PULMONARY SARCOIDOSIS: A RARE CLINICAL PRESENTATION

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sarcoidosis is a multi-systemic granulomatous disorder of unknown etiology and is characterized pathologically by the presence of non-caseating granulomas in involved organs; particularly in the lungs, hilar lymph nodes, skin, and eyes. Sarcoidosis affects individuals of any age, sex and race but it commonly affects young to middle-aged, Black American adults. The diagnosis of sarcoidosis is made on the basis of clinical features with compatible radiological findings and is further supported by the histological evidence non-caseating granulomas in affected organs, and the exclusion of other disorders that may present similarly. Biopsy is usually recommended for all patients that are suspected of having sarcoidosis with the exception of Lofgren's syndrome, Heerfordt syndrome and Lupus Pernio. Extra-pulmonary lymph nodes are present in 15% of patient's at the time of diagnosis. We present a young female who presents with bilateral inguinal lymphadenopathy as the first sign of sarcoidosis CASE PRESENTATION: A 32 year old female presented with complaints of bilateral, non-tender, inguinal swellings that progressively enlarged over a two week period. This was accompanied by a five pounds weight loss which she attributed to decreased appetite due to personal stressors. She had no associated fever, chills, vaginal discharge, dyspnea, cough, arthralgia or rashes. Physical examination revealed multiple, palpable, non-tender, mobile inguinal lymph nodes of varying sizes bilaterally with no associated overlying skin changes. She had no hepatomegaly, splenomegaly or uveitis. The erythrocyte sedimentation rate was 34 mm/hr (<25 mm/hr), 25 hydroxy-vitamin D was 13.5 ng/mL (30.0-80.0 ng/mL) and serum angiotensin converting enzyme level was 259 U/L (9.0-47.0 U/L). Abdomen and pelvic computed tomography showed bilateral inguinal lymphadenopathy measuring up to 1.6 cm on short axis. Chest computed tomography showed bulky mediastinal and bilateral hilar adenopathy with bilateral axillary lymphadenopathy. There were multifocal clusters of peri-lymphatic lung nodules in bilateral lungs. Excisional biopsy of the right inguinal lymph node revealed non-caseating granulomatous lymphadenitis. Acid fast bacilli (AFB) stain was negative for acid fast organisms. DISCUSSION: While extra-pulmonary manifestations of sarcoidosis are common, inguinal lymphadenopathy remains a rare presenting complaint with few documented cases. This finding suggests that biopsy of peripheral lymph nodes in an effort to establish the presence of granulomas, with the appropriate radiographic findings and clinical presentation, remains a viable and minimally invasive method of diagnosing sarcoidosis. CONCLUSIONS: The differential diagnosis for inguinal lymphadenopathy should include systemic conditions such as sarcoidosis. REFERENCE #1: Baughman, RP, Teirstein, AS, Judson, MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164: 1885–1889. REFERENCE #2: Monnet P, Thevenon J. Sarcoidosis with clinically isolated mediastinal adenopathy; diagnosis confirmed by biopsy of inguinal & right pre-scalenic lymph nodes. Lyon Med 1959;91:191-5. REFERENCE #3: Iannuzzi MC, Rybicki BA, Teirstein AS (2007) Sarcoidosis. N Engl J Med 357(21):2153–2165. DISCLOSURES: No relevant relationships by Sai Achi, source=Web Response No relevant relationships by Raji Ayinla, source=Web Response No relevant relationships by Janet Joseph, source=Web Response No relevant relationships by Richard Sheppard, source=Web Response

EP22 A manifestation of severe sarcoid arthropathy in the distal interphalangeal joint

In 2011 a gentleman in his 50s presented with nasal blockage and bloody discharge. He was diagnosed with sarcoidosis and after 9 years of failed strategies to control his disease, he developed dactylitis. X-ray of the hands showed severe arthropathy in the distal interphalangeal joints. This case demonstrates an uncommon extrapulmonary manifestation of sarcoidosis. Although most of his follow up was with a respiratory clinic, his main symptoms were not due to interstitial lung disease, highlighting the importance of a multidisciplinary approach. To reduce the need for steroids, several DMARDs were tried illustrating that there are limited treatment options.

DIAGNOSING SARCOIDOSIS IN THE EYE OF THE STORM

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Sarcoidosis is a granulomatous disease that typically affects the lungs but can involve all organ systems to a different extent and degree. The diagnosis requires a step wise approach that includes identifying affected organs amenable for biopsy. Up to 30% of patients may present with extra-pulmonary manifestations of sarcoidosis and ocular involvement is seen in up to 25% of these cases. We discuss a case of difficult to diagnose sarcoidosis in a patient with difficult to control asthma that presented with choroidal lesions concerning for ocular lymphoma which prompted additional workup. CASE PRESENTATION: 68 year-old woman with past medical history of difficult-to-treat, severe asthma and obesity with mixed restrictive/obstructive pulmonary functions referred to our institution for a second opinion. She had a long history of asthma since early in childhood that became very difficult to control requiring multiple burst of steroids, use of biologics, and high dose inhaled steroids. She endorsed daily productive cough of white sputum and mild malaise. She denied any other respiratory symptoms. She had undergone an extensive work including serologies and two bronchoscopies with transbronchial and endobronchial biopsies. Chest CT revealed patchy, ill-defined bilateral tree-in-bud opacities without bronchiectasis. Routine exam by her ophthalmologist prompted referral to a regional oncologic ophthalmologist and she was given the presumptive diagnosis of choroidal lymphoma and recommended to undergo choroid biopsy. A PET scan was positive only in the tonsillar beds and biopsy revealed reactive lymphoid hyperplasia. After discussion with ophthalmology the differential diagnosis of choroidal lymphoma, it was decided to proceed to a cryobiopsy of the lung to exclude the possibility of sarcoidosis. She underwent a bronchoscopy and bronchioalveolar lavage revealed 69% lymphocytes with normal flow cytometry. Cryobiopsy revealed non-necrotizing granulomas in a lymphangitic distribution without interstitial inflammation or bronchiolitis. After excluding other causes of granulomatous diseases coupled with eye lesions, patient was diagnosed with systemic sarcoidosis. She was started on oral prednisone with improvement in her respiratory symptoms. DISCUSSION: Sarcoidosis can present with mixed obstructive and restrictive physiology and mimic or exacerbate asthma. It can also present with both anterior and posterior uveitis and is the presenting symptom in 5% of cases. Choroidal and retinal disease can exist without symptoms yet result in blindness. CONCLUSIONS: It is important to recognize this potential presentation of sarcoidosis to start prompt treatment and prevent late complications such as secondary glaucoma and impaired vision. Reference #1: Y. Jamilloux, L. Kodjikian, C. Broussolle, P. Sève. Sarcoidosis and uveitis. Autoimmun Rev. 2014 Aug;13(8):840-9. Epub 2014 Apr 3. Reference #2: B. Bodaghi, V. Touitou, C. Fardeau, C. Chapelon, P. LeHoang. Ocular sarcoidosis. Presse Med, 41 (6 Pt 2) (2012), pp. e349-e354 Reference #3: M. Drent, U. Costabel. European respiratory monograph 32: sarcoidosis. European Respiratory Society (2005) DISCLOSURES: No relevant relationships by Sarah Hackman, source=Web Response No relevant relationships by Jay Peters, source=Web Response No relevant relationships by Jorge Villalpando, source=Web Response

EP20 Hypercalcaemia in sarcoidosis

Case report - IntroductionSarcoidosis often classically presents as Lofgren’s syndrome in up to 30% of cases, a triad of erythema nodosum, bilateral hilar lymphadenopathy and polyarthritis. However, the lack of identification and awareness of extrapulmonary manifestations of sarcoidosis can often lead to delayed diagnosis and treatment. In sarcoidosis, hypercalcaemia is a feature in only 10-20% of all cases. However, the manifestation of hypercalcaemia may be the first presentation of sarcoidosis in patients who do not show the classical features of acute sarcoidosis. Case report - Case descriptionA 38-year-old man presented with a 5-month history of profound fatigue, poor concentration, and non-specific joint pains. He reported earlier swelling of his ankles and feet. He had lost 1 stone in weight over the last month. There was no history of fever or night sweats. He smoked 10 cigarettes per day but was otherwise fit and well. On examination urine dipstick testing was negative. There was no evidence of lymphadenopathy. Cardio-respiratory and abdominal examinations were unremarkable. Examination of his skin and joints was also unremarkable. There was mild non-tender ankle oedema.His first blood tests showed a raised adjusted calcium of 3.25 and a raised white cell count of 11.8, with an eosinophilia of 0.75. Other preliminary blood results were unremarkable (normal Hb, U+Es, LFTs, CRP, ESR, RF, anti-CCP, ANA and TFTS). His chest X-ray was reported as clear.His PTH was appropriately suppressed and vitamin D level was adequate with normal urinary calcium and normal serum protein electrophoresis. Serum ACE level was raised at 114 (normal 8-52). PTH related peptide test was not available.A CT chest abdomen and pelvis scan carried out to rule out malignancy was normal with no notable lymphadenopathy. A subsequent PET CT scan was normal. Acutely, his hypercalcaemia was treated with IV fluids and IV pamidronate. Although his calcium rapidly normalised, he reported feeling only 10% better. He complained of ongoing ankle pain. An MRI scan of both ankles with contrast showed mild synovitis of ankle, subtalar and talonavicular joints. There was also evidence of tenosynovitis.Given the constellation of hypercalcaemia, raised serum ACE level and ankle synovitis on MRI scan, he was treated for sarcoidosis with prednisolone 20mg. This led to a rapid improvement in his symptoms and normalisation of serum ACE. He was started on azathioprine as a steroid-sparing agent. Case report - DiscussionIn cases series, hypercalcaemia due to sarcoidosis accounts for only 6% of all hypercalcaemic patients. The mechanism of hypercalcaemia in sarcoidosis is thought to be via activated pulmonary macrophages and sarcoid lymph node granulomas which upregulate the enzyme 1-alpha hydroxylase, resulting in the increased formation of calcitriol (1,25(OH)2D3). This increases calcium absorption from the gastrointestinal tract, stimulates renal calcium reabsorption and promotes calcium release from skeletal stores, causing hypercalcaemia.This case was particularly unusual as earlier literature suggests that sarcoidosis-associated hypercalcaemia is a result of activated pulmonary macrophages and sarcoid granulomas. However, this patient had significant hypercalcaemia without any radiological lung involvement or granulomata, posing the question whether there are other pathways causing hypercalcaemia in sarcoidosis. Hypercalcaemia without pulmonary involvement may be due to the presence of small amounts of sarcoid granulomata in extra-pulmonary locations such as the porta hepatis. These may not be as easily detectable on radiological investigations but may contribute to the upregulation of 1-alpha hydroxylase and subsequent hypercalcaemia. Another explanation for the significant hypercalcaemia in this patient may be due to the production of parathyroid hormone-related peptide (PTHrP) from sarcoid granulomas and bone marrow, which upregulates renal 1-alpha hydroxylase enzymes and increases the formation of calcitriol.There was no area to obtain a tissue biopsy given the normal CT and PET CT scans, resulting in a greater reliance on history, examination, and serological investigations. In addition, 30-50% of all patients with sarcoidosis have hypercalciuria, yet this patient interestingly had only an isolated hypercalcaemia with a normal urinary calcium. Case report - Key learning points Hypercalcaemia is rare in the absence of pulmonary involvement with only 10 cases reported in literature.Although non-specific, an elevated serum ACE level may be a useful pointer to the diagnosis of sarcoidosis in the absence of other classical signs.In this case, granulomatous tissue responsible to produce 1,25(OH)2D3 might be below the limits of radiological detection. Production may originate from extra-pulmonary sarcoid granulomatous tissue such as in the porta hepatis. Another possible mechanism for hypercalcaemia may be the production of PTHrP which has been reported in sarcoid tissue specimens and in the bone marrow.

Clinical and functional features of the course of respiratory sarcoidosis in real practice

As a rule, heart damage in patients with sarcoidosis of respiratory organs (SOD) is not diagnosed in time, so a very important and urgent task is to identify common heart rhythm and conduction disorders.The aim of the studywas to investigate the main clinical manifestations of sarcoidosis in SOD, depending on the peculiarities of the disease course and to compare the frequency and severity of pulmonary and extrapulmonary manifestations of sarcoidosis, including myocardial lesions and electrocardiographic (ECG) signs of heart rhythm disorders.Methods. In the period 2006– 2016, the pilot open prospective uncontrolled study conducted at the Pulmonology Department of the Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital" included patients (n = 84) aged 20–67 years with the diagnosis of SOD. Patients were divided into 2 clinical groups: the 1st comprised 45 (53.5%) patients with a favorable course of sarcoidosis, the second one included 39 (46.4%) patients with an unfavorable course of the disease. A full range of studies was carried out, including the analysis of medical history and clinical and epidemiological data, instrumental methods (including ECG and Holter ECG monitoring (HM), pathomorphological study of lung biopsy samples.Results. According to the data of frequency analysis of occurrence of pulmonary and extrapulmonary clinical manifestations in ODS, it was shown that the leading clinical manifestations, most frequently occurring in patients of both groups, included asthenia syndrome (72.6%), bronchial syndrome (66.7%) and fever syndrome (33%). In 33% of cases, clinical manifestations of myocardial damage were detected. In 41 (51.2%) patients in both groups, changes on ECG were recorded at rest. Regardless of the course of the disease, in 23.5% of patients of both clinical groups, according to the results of the HM ECG, rhythm and conduction disturbances were found – a combination of ventricular arrhythmias and conduction disorders (ventricular extrasystole and right His bundle branch block of various degrees) and a combination of supraventricular arrhythmias and conduction disturbances (supraventricular extrasystole and right His bundle branch block of various degrees).Conclusion. Thus, regardless of the severity of the disease course, SOD patients are concerned about complaints from both respiratory system and extrapulmonary manifestations, including cardiac complaints, as well as heart rhythm and conduction disorders (according to the results of ECG and HM ECG), the frequency of which, according to the comparative analysis, has not significantly changed in both clinical groups, which indicates the non-specific character of clinical manifestations.

Позалегеневі прояви саркоїдозу у дітей (лекція)

Позалегеневі прояви саркоїдозу у дітей (лекція)

Characteristics of sarcoidosis in Maori and Pacific Islanders.

Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity.

57-Year-Old Man With Hip Pain and Lytic Bone Lesions

57-year-old man presented to his primary care physician with a 2-year history of progressive right hip pain. His medical history was notable for hyperlipidemia. He was up-to-date on sex- and agespecific cancer screening. The patient had no history of chest pain, palpitations, shortness of breath, cough, or other cardiac, respiratory, neurologic, or visual symptoms. He had no recent travel history or occupational or social contact with persons who were ill. Physical examination revealed an obese man (body mass index [calculated as weight in kilograms divided by height in meters squared], 40.34 kg/m 2 ) with normal vital signs and unremarkable findings on cardiac, respiratory, abdominal, neurologic, and lymphatic examination. No pain or tenderness was elicited on examination. He was treated initially with nonopioid pain medications. Sacroiliac corticosteroid injections were minimally beneficial. Results of a complete blood cell count (CBC) and electrolyte panel were normal with the exception of an elevated serum calcium level of 11.7 mg/dL (reference range, 8.9-10.1 mg/dL). Ultimately, magnetic resonance imaging (MRI) of his lumbar spine revealed numerous punched-out lytic lesions in the lumbar vertebra and pelvis. He underwent computed tomography (CT) of his chest, abdomen, and pelvis that identified further lytic lesions as well as multiple splenic lesions concerning for metastases. Two separate CT-guided bone biopsy samples of the lytic lesions in the lumbar vertebra did not elicit an etiology of the lesions.

Acute Cholecystitis as an Extrapulmonary Manifestation of Sarcoidosis: A Rare Clinical Presentation

Sarcoidosis is a systemic granulomatous process of unknown cause. Pathologically, it is characterized by noncaseating granulomas, and in more than 90% of patients, the lungs are affected. In rarely involves the gallbladder. The finding of noncaseating granulomas is nondiagnostic as other granulomatous diseases are more likely to be found in the GI tract. Although rare, GI tract granulomas likely represent sarcoidosis when prior diagnosis is confirmed. We present a patient with acute cholecystitis secondary to sarcoidosis. A 66-year old male with a history of pulmonary sarcoidosis presented with intermittent biliary colic of two weeks. He admit to worsening right upper quadrant pain two days prior to admission, with nausea and vomiting related to meals. He denied changes in bowel movements, jaundice, or exposure to hepatotoxins. Medical history included untreated pulmonary sarcoid, as he was lost to follow-up after initial diagnosis. He denied prior surgeries, smoking, drug use, travel or new sexual partners. Localized tenderness below the right costal margin was present on physical exam. Laboratory studies disclosed normal CBC, lipase of 67, and normal liver function tests. HbsAg and AntiHCV were negative. ACE level was elevated 78 and calcium normal. Right upper quadrant ultrasound demonstrated cholelithiasis with gallbladder wall thickening suggestive of acute cholecystitis. The patient underwent laparoscopic cholecystectomy and symptoms resolved. During surgery, a dilated gallbladder and a large node of Calot, the sentinel lymph node of the gallbladder, were resected. Histologically, numerous noncaseating granulomas were found within the gallbladder and Calot's node. A diagnosis of extra-pulmonary sarcoidosis was confirmed. Sarcoidosis involving the gallbladder is not well described in the literature as it is rare. The involvement of Calot's node and extrinsic compression of the cystic duct by the granulomatous lymph node likely led to cholecystitis. Whether disease can regress spontaneously or with steroid therapy is unknown. There no confirmatory test for sarcoidosis and diagnosis involves excluding other causes of granulomatosis, such as infection. Crohn's was unlikely as pulmonary disease is statistically rare. It is important to consider sarcoidosis as a systemic syndrome. Gallbladder involvement, though rare, is important to consider in patients with a history of sarcoidosis and complaints suggestive of biliary colic.

Pulmonary and extra-pulmonary manifestations of sarcoidosis.

Background:Sarcoidosis is a systemic multi-organ granulomatous disease of unknown etiology that is characterized by the presence of granuloma in various organs. The clinical features of sarcoidosis are heterogeneous but pulmonary involvement is cardinal manifestations. The aim of this study was to determine radiologic, clinical and laboratory findings of patients with sarcoidosis.Patients and Methods:In a cross-sectional study, all patients visiting sarcoidosis clinic were enrolled in the study. Computed tomography (CT) scan was obtained and lab exams were obtained from patient and reports were recorded in data sheet.Results:Total of 55 patients with sarcoidosis were enrolled in the study. The average of age was 44.6 (range 25-62) years. Thirty-seven patients were male and 18 were female. The most common extra-pulmonary manifestation was arthritis (in 18% of cases) and then lupus pernio (12.8%) and uveitis (10.9%). Bilateral hilar adenopathy and para tracheal lymphadenopathy was observed in 39(70%) and 22 (40%) of patients. Parenchymal nodules (30%), bronchiectasia (25%), ground-glass opacification (18%) were the most common findings. Percentages of patients with dyspnea were 29% and percentages of patients with cough were 21%. Among abnormal lab tests, high urine calcium (Ca) were positive in 21% and high angiotensin-converting enzyme (ACE) in 16% of patients.Conclusion:Pulmonary involvements are both fibrosis and granulomatosis and the most common manifestations are parenchymal nodules, bronchiectasia and high-grade fibrosis. The most common extra-pulmonary involvement is arthritis. Lab tests are non-specific and have no correlation with duration or severity of disease.

Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis with interferon-β-1b: a case report

IntroductionSeveral cases of sarcoidosis following treatment with interferon-α have been reported in the literature, but those following interferon-β are very rare. We report the case of a patient with multiple sclerosis who developed pulmonary and cutaneous sarcoidosis following treatment with Betaseron® (interferon-β-1b).Case presentationA 33-year-old Caucasian woman with a history of multiple sclerosis, treated with interferon-β-1b for 2.5 years developed erythema nodosum in her lower limbs, a breast abscess, and unilateral adenopathy of her left lung. A skin biopsy confirmed sarcoidosis. After the discontinuation of interferon-β-1b and treatment with indomethacin and prednisolone, she recovered.ConclusionsSarcoidosis is considered one of the most common multiple sclerosis imitators with involvement of the central nervous system. However, although rare, sarcoidosis can develop following treatment with interferon-β-1b and should be considered in patients with multiple sclerosis treated with beta-interferons who develop pulmonary or extra-pulmonary manifestations of sarcoidosis. Interferon-β-1b discontinuation is the first and most important step in the treatment of such cases followed by treatment with corticosteroids.

Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy

IntroductionInfliximab, a humanized, chimeric, monoclonal antibody against tumor necrosis alpha (TNF-α), has been shown to reduce the pulmonary and extra-pulmonary manifestations of sarcoidosis, however, there is little information regarding sustained efficacy with long-term use of infliximab. We retrospectively investigate whether a reduction in disease response is maintained, over a prolonged course of therapy (up to 85 months) with infliximab, and report on adverse events associated with its use. MethodsSubjects with multi-organ sarcoidosis were prescribed infliximab, between January 2000 to June 2010 due to failure of conventional therapy and were identified from the Drexel University College of Medicine sarcoidosis clinic. Retrospective patient reported symptom and objective clinical data analyses of pulmonary and extra-pulmonary findings were evaluated pre-infliximab and post or concurrent infliximab therapy. Any adverse events or reasons for discontinuation during infliximab therapy were reported. ResultsTwenty-six patients with biopsy proven sarcoidosis received anti-TNF therapy and met the criteria for study inclusion. Clinical evidence of sustained resolution or improvement was demonstrated in 58.5% of all organs assessed (p =<0.001). No clinical change in disease activity was seen in 35.8% of all organs evaluated. Despite infliximab treatment, 5.7% had progressive disease activity. Adverse events were seen in 57.7% of patients treated with infliximab over a 46.2 month average duration of therapy. Three (12%) patients had an adverse event that required permanent discontinuation. ConclusionsInfliximab is efficacious in the treatment of extra-pulmonary sarcoidosis and the efficacy is maintained with prolonged treatment. In patients with pulmonary sarcoid, sustained improvement in pulmonary imaging was seen after initiation of infliximab, however, post-treatment pulmonary function testing was not conclusive. Long-term infliximab therapy was well tolerated for our study group.

Diaforodiagnostic dilemma of a breast tumor in a patient with known history of chest sarcoidosis: a diagnostic approach

Abstract Breast sarcoidosis is extremely rare, substantially less frequent than other extrapulmonary manifestations of sarcoidosis. It can mimic a benign or malignant tumor of the breast. We describe the case of a patient with a history of pulmonary sarcoidosis referred to our hospital for a screening mammography. Mammographic findings raised the suspicion for a breast mass. An additional breast ultrasound and fine -needle aspiration biopsy were performed. Finally, patient underwent a excisional biopsy of the left breast and the histopathological report revealed sarcoidosis.

Multiple myeloma with lacrimal gland amyloidosis and sarcoidosis

Our patient, a 46-year-old black woman, diagnosed with pulmonary sarcoidosis at bronchoscopy but without significant symptomatology for 14 years presented to her primary physician with marked bilateral upper eyelid swelling, conjunctival erythema, and dry eyes. Initial laboratory studies including chemistries, urinalysis, and complete blood count were normal. She was treated with topical ophthalmic steroids, because her symptoms and physical findings were thought to be extrapulmonary manifestations of sarcoidosis. Despite several weeks of treatment, her symptoms and physical findings persisted, and she was referred to an ophthalmologist. A computed tomography (CT) scan of the orbits was obtained and confirmed extensive bilateral enlargement of the lacrimal glands. The ophthalmologist concurred with the presumptive diagnosis of orbital sarcoidosis and continued topical treatment. Because of the patient's history of sarcoidosis, although she stated that she had no pulmonary symptoms, she was referred to pulmonary medicine for further clinical evaluation. She underwent radiography and high-resolution chest CT that showed patchy areas of central and peripheral honeycombing fibrosis in the upper lobes of both lungs without hilar adenopathy. These findings were consistent with radiographic Stage IV pulmonary sarcoidosis with multifocal fibrotic changes. Spirometry was normal without restrictive or obstructive abnormalities. Serum nuclear antibodies for Wegener granulomatosis were also negative.

Severe cholestatic granuloumatous hepatitis in sarcoidosis disease with minimal pulmonary involvement

Extrapulmonary manifestations of sarcoidosis are frequently reported. Liver involvement is usually inapparent, with only mild elevation of liver function tests, whereas progressive cholestasis and/or cirrhosis are rarely reported. Sarcoidosis prevalence differs among racial and ethnic groups, and it is known to affect blacks more acutely and more severely than it does people of other races. We report the case of a black nigerian 35-yr old woman, living in Italy since 1988, admitted because fever, itching and increased cholestatic liver tests (GT 1837 IU, ALP 3854 IU, total bilirubin 3.5 mg/dl, AST 71 IU, ALT 84 IU, Cholesterol 448 mg/dl). Abdominal US revealed gallstones and associated cholecystitis, and hepatosplenomegaly. She underwent laparoscopic cholecystectomy: during the procedure an enlarged lymph node close to the gallbladder was collected and a liver biopsy was performed. Histology showed multiple confluent non caseating granulomas, with epitheliod and multinucleated giant cells. All serological and antibodies tests, and microbiological cultures were negative. Chest X-ray, CT and HRCT were normal, whereas abdominal CT confirmed an important hepatosplenomegaly, with numerous hypodense nodular splenic lesions, and hepatic hilar-node enlargement. No significant pulmonary physiologic abnormalities were detected, nevertheless a broncoscopy was performed, with transbronchial lung biopsy and bronco-alveolar-lavage collections. Lung biopsies confirmed the presence of granulomatous involvement and the BAL showed a typical sarcoidosis pattern. Serum ACE (angiotensin-converting-enzyme) activity was 70 U/L. Corticosteroid therapy was started (prednisolone 50 mg daily, with gradual tapering of the dose), plus azatioprine (150 mg daily) and ursodeoxycholic acid (1350 mg daily). After six month of treatment transaminases, bilirubin and ACE levels were in the normal range, whereas GT and ALP decreased significantly (1249 and 1331, respectively). This single case of sarcoidosis presented to the clinician almost exclusively with liver disease; it confirms that in Africans the disease is characterized by more severe extrapulmonary involvement. The consideration of sarcoidosis in such cases is of utmost importance, since the differential diagnosis of hepatic granulomas includes infectious diseases in which treatment with corticosteroids could be fatal.